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B6-hLAG3

 

Strain Name: B6/JGpt-Lag3 emCin(hLAG3) /Gpt

Strain Type: Knock-in

Strain ID: T003597

Background: C57BL/6JGpt

 

Application

1. Efficacy evaluation of human LAG3 inhibitors

2. Safety evaluation of human LAG3 inhibitors

3. Anti-tumor Drug Research and Development

4. Research on autoimmune diseases

 

Description

LAG3(Lymphocyte activation gene 3), a cell surface molecule expressed on activated T cells, NK cells, B cells and plasmacytoid dendritic cells. Studies have shown that knock out the LAG3 gene or in vivo antibodies blocking LAG3 function can increase the aggregation and effector function of antigen-specific CD8+ T cells in organs or tumors, Therefore, blocking LAG3 is a potential tumor treatment. B6-hLAG3 mice the ideal animal model to evaluate the efficacy of human LAG3 antibody.

 

Data support

Detection of LAG3 expression

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hLAG3 homozygous mice expressed human LAG3 on both T and B cell surfaces.

T/B/NK cell ratio assay

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The proportion of T/B/NK cells in B6-hLAG3 homozygous, heterozygous and wild type mice was basically the same.

Anti-tumor Efficacy Test

Evaluation of in vivo efficacy of Anti-hLAG3 by subcutaneous inoculation of MC38 model in B6-hLAG3 mice

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Fig.4 In vivo efficacy test based on B6-hLAG3.

   Murine colon cancer MC38 cells was cultured to logarithmic growth phase and inoculated subcutaneously into 6-8 weeks old B6-hLAG3 mice. Mice were divided into Vehicle groups, Anti-mPD1 groups, Anti-LAG3 groups and Anti-mPD1 + Anti-hLAG3 groups (n=6).When the tumor size reached about 100 mm3, mice were treated with the appropriate medication twice a week for a total of 6 times. Data are presented in Mean ± SEM format. 

Result:Anti-mPD1 group, Anti-mPD1 group inhibit tumor growth, and Anti-mPD1 + Anti-hLAG3 group inhibited tumor growth (TGI = 19.13%, TGI = 21.13% and TGI = 40.69% respectively)(Fig.4, Left). The trend of weight change of different group is consistent (Fig.4,Right). The data indicated that B6-hLAG3 mice is the ideal animal model to evaluate the efficacy of human LAG3 antibody.

References

1. Sierro, Sophie, Pedro Romero, and Daniel E. Speiser. "The CD4-like molecule LAG-3, biology and therapeutic applications." Expert opinion on therapeutic targets 15.1 (2011): 91-101. 

2. Goldberg, Monica V., and Charles G. Drake. "LAG-3 in cancer immunotherapy." Cancer Immunology and Immunotherapy. Springer, Berlin, Heidelberg, 2010. 269-278. 

3. Triebel, Frederic, et al. "LAG-3, a novel lymphocyte activation gene closely related to CD4." Journal of Experimental Medicine 171.5 (1990): 1393-1405.

4. Huard, Bertrand, et al. "CD4/major histocompatibility complex class II interaction analyzed with CD4and lymphocyte activation gene3 (LAG3)Ig fusion proteins." European journal of immunology 25.9 (1995): 2718-2721. 

5. Hannier, Sigrid, et al. "CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling." The Journal of Immunology 161.8 (1998): 4058-4065.

6. Hannier, Sigrid, and Frédéric Triebel. "The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3–TCR molecules after their engagement by mAb or peptide–MHC class I complexes." International immunology11.11 (1999): 1745-1752.

7. Grosso, Joseph F., et al. "LAG-3 regulates CD8+ T cell accumulation and effector function in murine self-and tumor-tolerance systems." The Journal of clinical investigation117.11 (2007): 3383-3392.


Time:2020-01-14

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